Our findings suggest an important between- and within-sex role of absolute handgrip strength in mediating the BP response to static handgrip exercise and highlight the importance of controlling for interindividual differences in future work.

Ischemic preconditioning (IPC) has been hypothesized to elicit ergogenic effects by reducing feedback from metabolically sensitive group III/IV muscle afferents during exercise. If so, reflex efferent neural outflow should be attenuated. We investigated the effects of IPC on muscle sympathetic nerve activity (MSNA) during static handgrip (SHG) and used post‐exercise circulatory occlusion (PECO) to isolate for the muscle metaboreflex. Thirty‐seven healthy men (age: 24 ± 5 years [mean ± SD]) were randomized to receive sham (n = 16) or IPC (n = 21) interventions. Blood pressure, heart rate, and MSNA (microneurography; sham n = 11 and IPC n = 18) were collected at rest and during 2 min of SHG (30% maximal voluntary contraction) and 3 min of PECO before (PRE) and after (POST) sham or IPC treatment (3 × 5 min 20 mmHg or 200 mmHg unilateral upper arm cuff inflation). Resting mean arterial pressure was higher following sham (79 ± 7 vs. 83 ± 6 mmHg, P < 0.01) but not IPC (81 ± 6 vs. 82 ± 6 mmHg, P > 0.05), while resting MSNA burst frequency was unchanged (P > 0.05) with sham (18 ± 7 vs. 19 ± 9 bursts/min) or IPC (17 ± 7 vs. 19 ± 7 bursts/min). Mean arterial pressure, heart rate, stroke volume, cardiac output, and total vascular conductance responses during SHG and PECO were comparable PRE and POST following sham and IPC (All P > 0.05). Similarly, MSNA burst frequency, burst incidence, and total MSNA responses during SHG and PECO were comparable PRE and POST with sham and IPC (All P > 0.05). These findings demonstrate that IPC does not reduce hemodynamic responses or central sympathetic outflow directed toward the skeletal muscle during activation of the muscle metaboreflex using static exercise or subsequent PECO.

PurposeLarger blood pressure (BP) responses to relative-intensity static exercise in men versus women are thought to involve altered muscle metaboreflex activation, but whether this is because of an intrinsic sex difference in metabolite production or differences in muscle strength and absolute load is unknown.MethodsContinuous BP and heart rate were recorded in 200 healthy young men and women (women: n = 109) during 2 min of static handgrip exercise at 30% of maximal voluntary contraction (MVC), followed by 2 min of postexercise circulatory occlusion (PECO). Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (n = 39; women, n = 21), permitting calculation of signal-averaged resting sympathetic transduction (MSNA-diastolic BP). Sex differences were examined with and without statistical adjustment for MVC. Multivariate regression analyses were performed to identify predictors of BP responses.ResultsMen had larger systolic BP responses (interactions, P < 0.0001) to static handgrip exercise (24 ± 10 vs 17 ± 9 mm Hg [mean ± SD], P < 0.0001) and PECO (20 ± 11 vs 16 ± 9 mm Hg, P < 0.0001). Adjustment for MVC abolished these sex differences in BP (interactions, P > 0.7). In the subset with MSNA, neither burst frequency or incidence responses to static handgrip exercise or PECO differed between men and women (interactions, P > 0.2). Resting sympathetic transduction was also similar (P = 0.8). Multiple linear regression analysis showed that MVC or the change in MSNA, were predictors of BP responses to static handgrip, but only MVC was associated with BP responses during PECO.ConclusionsSex differences in absolute contraction load contribute to differences in BP responses during muscle metaboreflex isolation using PECO. These data do not support an intrinsic effect of sex as being responsible for exercise BP differences between men and women.

Two subpopulations of muscle sympathetic single units with opposite discharge characteristics have been identified during low-level cardiopulmonary baroreflex loading and unloading in middle-aged adults and patients with heart failure. The present study sought to determine whether similar subpopulations are present in young healthy adults during cardiopulmonary baroreflex unloading ( study 1) and rhythmic handgrip exercise ( study 2). Continuous hemodynamic and multiunit and single unit muscle sympathetic nerve activity (MSNA) data were collected at baseline and during nonhypotensive lower body negative pressure (LBNP; n = 12) and 40% maximal voluntary contraction rhythmic handgrip exercise (RHG; n = 24). Single unit MSNA responses were classified as anticipated or paradoxical based on whether changes were concordant or discordant with the multiunit MSNA response, respectively. LBNP and RHG both increased multiunit MSNA burst frequency (∆5 ± 3 bursts/min, P < 0.001; ∆5 ± 8 bursts/min, P = 0.005), burst amplitude (∆5 ± 7%, P = 0.04; ∆13 ± 14%, P < 0.001), and total MSNA (∆302 ± 191 AU/min, P = 0.001; ∆585 ± 556 AU/min, P < 0.001). During LBNP and RHG, 43 and 64 muscle single units were identified, respectively, which increased spike frequency (∆9 ± 11 spikes/min, P < 0.001; ∆10 ± 19 spikes/min, P < 0.001) and the probability of multiple spike firing (∆10 ± 12%, P < 0.001; ∆11 ± 26%, P = 0.001). During LBNP and RHG, 36 (84%) and 39 (61%) single units possessed anticipated firing responses (∆12 ± 10 spikes/min, P < 0.001; ∆19 ± 19 spikes/min, P < 0.001), whereas 7 (16%) and 25 (39%) single units exhibited paradoxical reductions (∆−3 ± 1 spikes/min, P = 0.003; ∆−4 ± 5 spikes/min, P < 0.001). The observation of divergent subpopulations of muscle sympathetic single units in healthy young humans during two mild sympathoexcitatory stressors supports differential control at the fiber level as a fundamental characteristic of human sympathetic regulation. NEW & NOTEWORTHY The activity of muscle sympathetic single units was recorded during cardiopulmonary baroreceptor unloading and rhythmic handgrip exercise in young healthy humans. During both stressors, the majority of single units (84% and 61%) exhibited anticipated behavior concordant with the integrated muscle sympathetic response, whereas a smaller proportion (16% and 39%) exhibited paradoxical sympathoinhibition. These results support differential control of postganglionic muscle sympathetic fibers as a characteristic of human sympathetic regulation during mild sympathoexcitatory stress. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/differential-control-of-sympathetic-outflow-in-young-humans/ .

Purpose: Males have larger blood pressure (BP) responses to relative-intensity static handgrip exercise compared with females. Controlling for absolute load (maximal voluntary contraction (MVC)) abolishes these differences. Whether similar observations exist during large muscle mass exercise or dynamic contractions, and the mechanisms involved, remains unknown. Methods: BP, heart rate, muscle oxygenation (near-infrared spectroscopy), and rectus femoris EMG were recorded in 28 males and 17 females during 10% and 30% MVC static (120 s) and isokinetic dynamic (180 s; 1:2 work-to-rest ratio; angular velocity, 60°•s −1 ) knee extensor exercise. Static and dynamic exercises were completed on separate visits, in a randomized order. Sex differences were examined with and without statistical adjustment of MVC (ANCOVA). Results: Males had larger systolic BP responses (interaction, P < 0.0001) and muscle deoxygenation (interaction, P < 0.01) than did females during 10% static exercise, with no difference in EMG (interaction, P = 0.67). Peak systolic BP was correlated with MVC (r = 0.55, P = 0. 0001), and adjustment for MVC abolished sex differences in systolic BP (interaction, P = 0.3). BP, heart rate, muscle oxygenation/deoxygenation, and EMG responses were similar between sexes during 30% static exercise (interaction; all, P > 0.2), including following adjustment for MVC (all, P > 0.1). Males had larger systolic BP responses during dynamic exercise at 10% and 30% (interaction; both, P = 0.01), which were abolished after adjustment for MVC (interaction; both, P > 0.08). Systolic BP responses were correlated with absolute MVC and stroke volume responses during 10% (r = 0.31, P = 0.04; r = 0.61, P < 0.0001, respectively) and 30% (r = 0.48, P = 0.001; r = 0.59, P < 0.0001, respectively). Conclusions: Absolute contraction intensity can influence systolic BP responses to 10% but not 30% MVC static, as well as 10% and 30% MVC dynamic knee extensor exercise, and should be considered in cross-sectional comparisons of exercise BP.

Supplementation with monounsaturated or ω-3 polyunsaturated fatty acids ( n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and the mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-wk, randomized, double-blind trial examining the effects of orally supplementing ~3 g/day of EPA ( n = 28), DHA ( n = 28), or OO ( n = 30) on resting hemodynamics; MSNA was examined in a subset of participants ( n = 31). Both EPA and DHA supplements increased the ω-3 index ( P < 0.01). Reductions in systolic BP were greater [adjusted intergroup mean difference (95% confidence interval)] after DHA [−3.4 mmHg (−0.9, −5.9), P = 0.008] and OO [−3.0 mmHg (−0.5, −5.4), P = 0.01] compared with EPA, with no difference between DHA and OO ( P = 0.74). Reductions in diastolic BP were greater following DHA [−3.4 mmHg (−1.3,−5.6), P = 0.002] and OO [−2.2 mmHg (0.08,−4.3), P = 0.04] compared with EPA. EPA increased heart rate compared with DHA [4.2 beats/min (−0.009, 8.4), P = 0.05] and OO [4.2 beats/min, (0.08, 8.3), P = 0.04]. MSNA burst frequency was higher after DHA [4 bursts/min (0.5, 8.3), P = 0.02] but not OO [−3 bursts/min (−6, 0.6), P = 0.2] compared with EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA, but not OO, increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic overactivation. NEW & NOTEWORTHY We studied the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and olive oil supplementation on blood pressure (BP) and muscle sympathetic nerve activity (MSNA). After 12 wk of 3 g/day supplementation, DHA and olive oil were associated with lower resting systolic and diastolic BPs than EPA. However, DHA increased MSNA compared with EPA. The reductions in BP with DHA likely occur via a vascular mechanism and evoke a baroreflex-mediated increase in sympathetic activity.

Key points The arterial baroreflex controls vasoconstrictor muscle sympathetic nerve activity (MSNA) in a negative feedback manner by increasing or decreasing activity during spontaneous blood pressure falls or elevations, respectively. Spontaneous sympathetic baroreflex sensitivity is commonly quantified as the slope of the relationship between MSNA burst incidence or strength and beat‐to‐beat variations in absolute diastolic blood pressure. We assessed the relationships between blood pressure inputs related to beat‐to‐beat blood pressure change or blood pressure rate‐of‐change (variables largely independent of absolute pressure) and MSNA at rest and during exercise and mental stress. The number of participants with strong linear relationships between MSNA and beat‐to‐beat diastolic blood pressure change variables or absolute diastolic blood pressure were similar at rest, although during stress the beat‐to‐beat diastolic blood pressure change variables were superior. Current methods may not fully characterize the capacity of the arterial baroreflex to regulate MSNA. Abstract Spontaneous sympathetic baroreflex sensitivity (sBRS) is commonly quantified as the slope of the relationship between variations in absolute diastolic blood pressure (DBP) and muscle sympathetic nerve activity (MSNA) burst incidence or strength. This relationship is well maintained at rest but not during stress. We assessed whether sBRS could be calculated at rest and during stress (static handgrip, rhythmic handgrip, mental stress) using blood pressure variables that quantify relative change: beat‐to‐beat DBP change (ΔDBP), ΔDBP rate‐of‐change (ΔDBP rate), pulse pressure (PP) and PP rate‐of‐change (PP rate). Sixty‐six healthy participants underwent continuous measures of blood pressure (finger photoplethysmography) and multi‐unit MSNA (microneurography). At rest, absolute DBP (91%), ΔDBP (97%) and ΔDBP rate (97%) each yielded higher proportions of participants with strong linear relationships (r ≥ 0.6) with MSNA burst incidence compared to PP (57%) and PP rate (56%) and produced similar sBRS slopes (DBP: −4.5 ± 2.0 bursts 100 heartbeats–1/mmHg; ΔDBP: −5.0 ± 2.1 bursts 100 heartbeats–1/ΔmmHg; ΔDBP rate: −4.9 ± 2.2 bursts 100 heartbeats–1/ΔmmHg s–1; P > 0.05). During stress, ΔDBP (74%) and ΔDBP rate (74%) yielded higher proportions of strong linear relationships with MSNA burst incidence than absolute DBP (43%), PP (46%) and PP rate (49%) (all P < 0.05). The absolute DBP associated with a 50% chance of a MSNA burst (T50) was shifted rightward during static handgrip (Δ+15 ± 11 mmHg, P < 0.001) and mental stress (Δ+11 ± 7 mmHg, P < 0.001); however, the ΔDBP T50 was shifted rightward during static handgrip (Δ+2.5 ± 3.7 mmHg, P = 0.009) but not mental stress (Δ0.0 ± 4.4 mmHg, P = 0.99). These findings suggest that calculating sBRS using absolute DBP alone may not adequately characterize arterial baroreflex regulation of MSNA, particularly during stress.

Calculating the blood pressure (BP) response to a burst of muscle sympathetic nerve activity (MSNA), termed sympathetic transduction, may be influenced by an individual's resting burst frequency. We examined the relationships between sympathetic transduction and MSNA in 107 healthy males and females and developed a normalized sympathetic transduction metric to incorporate resting MSNA. Burst-triggered signal-averaging was used to calculate the peak diastolic BP response following each MSNA burst (sympathetic transduction of BP) and following incorporation of MSNA burst cluster patterns and amplitudes (sympathetic transduction slope). MSNA burst frequency was negatively correlated with sympathetic transduction of BP (r=-0.42; P<0.01) and the sympathetic transduction slope (r=-0.66; P<0.01), independent of sex. MSNA burst amplitude was unrelated to sympathetic transduction of BP in males (r=0.04; P=0.78), but positively correlated in females (r=0.44; P<0.01) and with the sympathetic transduction slope in all participants (r=0.42; P<0.01). To control for MSNA, the linear regression slope of the log-log relationship between sympathetic transduction and MSNA burst frequency was used as a correction exponent. In sub-analysis of males (38±10 vs. 14±4bursts/min) and females (28±5 vs. 12±4bursts/min) with high vs. low MSNA, sympathetic transduction of BP and sympathetic transduction slope were lower in participants with high MSNA (all P<0.05). In contrast, normalized sympathetic transduction of BP and normalized sympathetic transduction slope were similar in males and females with high vs. low MSNA (all P>0.22). We propose that incorporating MSNA burst frequency into the calculation of sympathetic transduction will allow comparisons between participants with varying levels of resting MSNA.